A Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Single and Multiple Ascending Doses of GDC-0334 and the Effect of Food on the Pharmacokinetics of GDC-0334 in Healthy Adult Participants

NCT03381144 | Terminated Phase 1

• 2 other identifiers: GB402232017-003498-33
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, single-center, three-part study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of single and multiple ascending doses of GDC-0334 and the effect of food on the pharmacokinetics of GDC-0334 in healthy adult participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants with Adverse Events

  From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days)

• Severity of Adverse Events, as Graded per the World Health Organization (WHO) Toxicity Grading Scale

  From signing of informed consent until 30 days after the last dose of study drug (Up to approximately 42 days)

• Change from Baseline in Blood Pressure

  Up to approximately 42 days

• Change from Baseline in Heart Rate

  Up to approximately 42 days

• Incidence of Electrocardiogram (ECG) Abnormalities

  Up to approximately 42 days

• Incidence of Clinical Laboratory Abnormalities

  Up to approximately 30 days

• Incidence of Physical Examination Abnormalities

  Up to approximately 42 days

• Incidence of Neurological Examination Abnormalities

  Up to approximately 31 days

• Columbia-Suicide Severity Rating Scale (C-SSRS) - Part 3 Only

  Up to approximately 42 days

Secondary Outcomes (9)

• Elapsed Time from Dosing at Which GDC-0334 is First Quantifiable in a Concentration versus Time profile (Tlag )

  Up to approximately 35 days

• Time to Maximum Plasma Concentration (Tmax) for GDC-0334

  Up to approximately 35 days

• Maximum Observed Plasma Concentration (Cmax) for GDC-0334

  Up to approximately 35 days

• Concentration at 24 hours Post-dose (C24) for GDC-0334

  Up to approximately 35 days

• Concentration at 12 hours Post-dose (C12) for GDC-0334

  Up to approximately 35 days

Study Arms (6)

Part 1: GDC-0334

EXPERIMENTAL

Participants in up to 7 cohorts will receive single, ascending doses of GDC-0334 under fasting conditions.

Drug: GDC-0334

Part 1: Placebo

PLACEBO COMPARATOR

Participants in up to 7 cohorts will receive single doses of placebo under fasting conditions.

Drug: Placebo

Part 2: GDC-0334

EXPERIMENTAL

Participants in up to 3 cohorts will receive single doses of GDC-0334 under fasting or fed conditions.

Drug: GDC-0334

Part 2: Placebo

PLACEBO COMPARATOR

Participants in up to 3 cohorts will receive single doses of placebo under fasting or fed conditions.

Drug: Placebo

Part 3: GDC-0334

EXPERIMENTAL

Participants in up to 4 cohorts will receive multiple, ascending doses of GDC-0334 under fasting or fed conditions.

Drug: GDC-0334

Part 3: Placebo

PLACEBO COMPARATOR

Participants in up to 4 cohorts will receive multiple doses of placebo under fasting or fed conditions.

Drug: Placebo

Interventions

GDC-0334 DRUG

Part 1: GDC-0334 given orally with dose escalation between cohorts, based on emerging safety and pharmacokinetic (PK) data. Parts 2 and 3: doses to be based on the safety, tolerability, and PK data generated in the study. The dosing duration in Part 3 is planned to be at least 14 days, but no longer than 28 days.

Part 1: GDC-0334; Part 2: GDC-0334; Part 3: GDC-0334

Placebo DRUG

Participants will receive GDC-0334-matching placebo.

Part 1: Placebo; Part 2: Placebo; Part 3: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or non-pregnant, non-lactating healthy females. Females may be of non-childbearing potential or childbearing potential. Healthy females of childbearing potential must agree to use a highly effective method of contraception.
• Healthy males must agree to use an adequate method of contraception
• Body mass index of 18.0 to 32.0 kilograms per meter squared (kg/m\^2) or, if outside the range, considered not clinically significant by the investigator
• Must be willing and able to communicate and participate in the whole study

You may not qualify if:

• Participants who have received any investigational medicinal product in a clinical research study within the previous 3 months
• Participants who are study site employees, or immediate family members of a study site or sponsor employee
• Participants who have previously been enrolled in this study. Participants who have enrolled in Part 1 are not permitted to enrol in Parts 2 or 3, and participants who have enrolled in Part 2 are not permitted to enroll in Part 3
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption \>14 units per week (1 unit = ½ pint beer, 25 milliliters (mL) of 40% spirit or a 125-mL glass of wine)
• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 6 parts per million (ppm) at screening or admission
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Participants who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening
• Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator
• Positive drugs-of-abuse test result at screening or admission
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) results
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of \<70 milliliters per minute (mL/min) using the Cockcroft-Gault equation
• History of seizure
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder, as judged by the investigator
• Participants with a history of cholecystectomy or gall stones (applies to any regimen where food effect is being explored)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (1)

Quotient Clinical Ltd, Clinical Research Unit

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

GDC-0334

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 21, 2017
• Study Start: December 8, 2017
• Primary Completion: April 29, 2019
• Study Completion: April 29, 2019
• Last Updated: October 18, 2019

Record last verified: 2019-10

Locations

GB (1)